Mischo Axel, Kubuschok Boris, Ertan Kubilay, Preuss Klaus-Dieter, Romeike Bernd, Regitz Evi, Schormann Claudia, de Bruijn Diederik, Wadle Andreas, Neumann Frank, Schmidt Werner, Renner Christoph, Pfreundschuh Michael
Department of Internal Medicine I, University of Saarland Medical School, Homburg/Saar, Germany.
Int J Cancer. 2006 Feb 1;118(3):696-703. doi: 10.1002/ijc.21352.
To determine the expression of cancer testis (CT) genes and antibody responses in a nonselected population of patients with primary breast cancer, we investigated the composite expression of 11 CT genes by RT-PCR in fresh biopsies of 100 consecutive cases of primary breast carcinoma and by immunohistology in selected RT-PCR-positive cases. Antibody responses against 7 CT antigens were analyzed using recombinant antigen expression on yeast surface. In 98 evaluable cases, SCP-1 and SSX-4 were expressed most frequently (both 65%), followed by HOM-TES-85/CT-8 (47%), GAGE (26%), SSX-1 (20%), NY-ESO-1 (13%), MAGE-3 (11%), SSX-2 (8%), CT-10 (7%), MAGE-4 (4%) and CT-7 (1%). One CT gene was expressed by 90% of the cases; 79% expressed > or =2, 48% > or =3, 29% > or =4, 12% > or =5, 6% > or =6, 3% > or =7, 2% > or =8 and one case coexpressed 9 antigens. Of 100 serum samples screened for CT antigen-specific antibodies, antibodies against NY-ESO-1 were detected in 4 patients, against SCP-1 in 6 patients and against SSX-2 in 1 patient, while no antibodies were detected against MAGE-3, CT-7 and CT-10. Expression of CT genes or antibody responses was not correlated with clinical parameters (menopausal status, tumor size, nodal involvement, grading, histology and estrogen receptor status) or the demonstration of CT gene expression at the protein level, by immunohistology. Our results show that breast carcinomas are among the tumors with the most frequent expression of CT antigens, rendering many patients potential candidates for vaccine trials.
为了确定原发性乳腺癌患者非选择人群中癌睾丸(CT)基因的表达及抗体反应,我们通过逆转录聚合酶链反应(RT-PCR)检测了100例连续原发性乳腺癌新鲜活检组织中11种CT基因的复合表达情况,并对部分RT-PCR阳性病例进行了免疫组织化学检测。利用酵母表面重组抗原表达分析了针对7种CT抗原的抗体反应。在98例可评估病例中,SCP-1和SSX-4表达最为频繁(均为65%),其次是HOM-TES-85/CT-8(47%)、GAGE(26%)、SSX-1(20%)、NY-ESO-1(13%)、MAGE-3(11%)、SSX-2(8%)、CT-10(7%)、MAGE-4(4%)和CT-7(1%)。90%的病例表达一种CT基因;79%表达≥2种,48%表达≥3种,29%表达≥4种,12%表达≥5种,6%表达≥6种,3%表达≥7种,2%表达≥8种,1例病例共表达9种抗原。在筛查的100份血清样本中,4例患者检测到针对NY-ESO-1的抗体,6例患者检测到针对SCP-1的抗体,1例患者检测到针对SSX-2的抗体,而未检测到针对MAGE-3、CT-7和CT-10的抗体。CT基因表达或抗体反应与临床参数(绝经状态、肿瘤大小、淋巴结受累情况、分级、组织学和雌激素受体状态)或免疫组织化学在蛋白水平上CT基因表达的显示均无相关性。我们的结果表明,乳腺癌是CT抗原表达最频繁的肿瘤之一,这使得许多患者成为疫苗试验的潜在候选者。